Mitochondrial membrane potential and delayed graft function following kidney transplantation

Jacqueline Garonzik, Bonnie E. Lonze, Jessica M. Ruck, Xun Luo, Allan B Massie, Keith Melancon, James F. Burdick, Dorry Segev, Zhao Li Sun

Research output: Contribution to journalArticle

Abstract

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P =.002) and donation after cardiac death donors (75% vs 12%, P =.004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Delayed Graft Function
Mitochondrial Membrane Potential
Kidney Transplantation
Tissue Donors
Kidney
Allografts
Registries
Health
Organ Transplantation
Counseling
Length of Stay
Ischemia
Perfusion
Odds Ratio
Transplants

Keywords

  • basic (laboratory) research/science
  • cytotoxicity
  • donors and donation: deceased
  • kidney (allograft) function/dysfunction
  • kidney transplantation/nephrology
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

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title = "Mitochondrial membrane potential and delayed graft function following kidney transplantation",
abstract = "Delayed graft function (DGF) complicates 20{\%}-40{\%} of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75{\%} vs 10{\%}, P =.002) and donation after cardiac death donors (75{\%} vs 12{\%}, P =.004). For every 10{\%} decrease in MMP levels, there were 38{\%} higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.",
keywords = "basic (laboratory) research/science, cytotoxicity, donors and donation: deceased, kidney (allograft) function/dysfunction, kidney transplantation/nephrology, translational research/science",
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AU - Garonzik, Jacqueline

AU - Lonze, Bonnie E.

AU - Ruck, Jessica M.

AU - Luo, Xun

AU - Massie, Allan B

AU - Melancon, Keith

AU - Burdick, James F.

AU - Segev, Dorry

AU - Sun, Zhao Li

PY - 2018/1/1

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N2 - Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P =.002) and donation after cardiac death donors (75% vs 12%, P =.004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

AB - Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P =.002) and donation after cardiac death donors (75% vs 12%, P =.004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.081.381.78, P =.01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

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